Glucocorticoids and Bone in Graves' Ophthalmopathy

The Effect of 4.5 Gram Methylprednisolone Administered Once Weekly for 12 Weeks on Bone Metabolism in Graves´ Ophthalmopathy

Continuous use of systemic glucocorticoids decreases bone mineral density and increases fracture risk. Graves' orbitopathy is treated with weekly infusion of high-dose intravenous glucocorticoid. The investigators aim at investigating whether this treatment regimen also affects bone metabolism.

Study Overview

• Status: Completed
• Conditions: Graves Ophthalmopathy
• Intervention / Treatment: Drug: Methylprednisolone

Detailed Description

Systemic glucocorticoid increases bone resorption and decreases bone formation and thereby decreases bone mineral density and increases fracture risk. This effect is evident with a daily dose of 5 mg for three months or an accumulated dose of 450mg. There is, however, less evidence that intermittent use of glucocorticoids is harmful to bone.

Graves orbitopathy is treated with a weekly infusion of the glucocorticoid methylprednisolone and the accumulated dose over a 12-week course sums up to 4,500mg.

The investigators therefore want to investigate if that treatment regimen affects bone turnover, bone mineral density, or bone structure in 30 patients with Graves' orbitopathy.

• Study Type: Observational
• Enrollment (Actual): 39

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5000C
    • Odense University Hospital
  • Central Denmark Region
    • Aarhus C, Central Denmark Region, Denmark, 8000
      • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

30 adult patients with Graves' Ophthalopathy

Description

Inclusion Criteria:

• Graves Ophthalmopathy that requires treatment with intra-venous methylprednisolone

Exclusion Criteria:

• Treatment with osteoporosis medication
• Primary hyperparathyroidism
• Hypoparathyroidism
• Vitamin D < 20mmol/L
• Estimated glomerular filtration rate < 30 mL/min
• Liver disease
• Peroral treatment with glucocorticoids within last three months prior to inclusion

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients; 30 patients with Graves' ophthalmopathy in which treatment with intravenous methylprednisolone is indicated	Drug: Methylprednisolone; Intravenous methylprednisolone; Other Names: Solu Medrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change Lumbar Spine Bone Mineral Density	Percent change in lumbar spine bone mineral density from baseline to week 12	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change Femoral Neck Bone Mineral Density	Percent change in femoral neck bone mineral density from baseline to week 12	12 weeks
Percent Change Total Hip Bone Mineral Density	Percent change in total hip bone mineral density from baseline to week 12	12 weeks
Bone Resorption	Change in bone resorption measured by the biochemical marker C-terminal telopeptide of type 1 collagen (CTx) where higher measures show increased bone resorption that decreases bone mineral density and strength.	12 weeks
Bone Formation	Change in Bone Formation Measured by the Biochemical Marker procollagen type I N-propeptide (P1NP) where higher measures in combination with increased CTx (see measure 4) show increased bone resorption that decrease bone mineral density and strength but where lower levels may suggest decreased bone formation that may alsodecrease bone mineral density and strength.	12 weeks
Percent Change in Bone Structure at the Radius	Percent change in radial cortical volumteric BMD measured by high-resolution peripheral quantitative computed tomography	12 weeks
Percent Change in Bone Structure at the Tibia	Percent change in tibial cortical volumetric BMD measured by high-resolution peripheral quantitative computed tomography	12 weeks

Collaborators and Investigators

• Sponsor: Torben Harsløf
• Collaborators: Odense University Hospital
• Investigators: Principal Investigator: Torben Harsløf, MD, PhD, University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2017
• Primary Completion (Actual): July 14, 2022
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: April 18, 2017
• First Submitted That Met QC Criteria: April 20, 2017
• First Posted (Actual): April 21, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 26, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Genetic Diseases, Inborn; Autoimmune Diseases; Immune System Diseases; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Thyroid Diseases; Eye Diseases; Graves Ophthalmopathy; Antineoplastic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Neuroprotective Agents; Methylprednisolone Acetate; Prednisolone; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: GRO-BONE1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No